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BUFFALO, N.Y. -- University at Buffalo researchers are
expressing concern about a new, under-recognized, much more potent
variant of a common bacterium that has surfaced in the U.S.

"Historically, in Western countries, classical strains of
Klebsiella pneumoniae have caused infections mostly in sick,
hospitalized patients whose host defense systems are compromised,"
says Thomas Russo, MD, professor in the Department of Medicine at
the UB School of Medicine and Biomedical Sciences and head of its
Infectious Disease Division.

"But in the last 10 to 15 years, a new variant of it has begun
causing community-acquired infection in young, healthy
individuals," he says. "This variant causes serious,
life-threatening, invasive infections and is able to spread to
other organs from the initial site of infection."

Perhaps most important, says Russo, these hypervirulent strains
of Klebsiella pneumoniae have the potential to become highly
resistant to antibiotics, similar to Escherichia coli and
classical Klebsiella pneumoniae.

"These hypervirulent strains are the next 'superbugs'
–in-waiting," he says. "If they become resistant to
antibiotics, they will become difficult, if not impossible to
treat."

With recent funding from the National Institutes of Health under
a program to fund high-risk, high-reward research, Russo and his UB
colleagues are studying the microbiology of the new variant of
Klebsiella pneumoniae in an effort to identify the genes
that make it hypervirulent so they can figure out how to stop it in
its tracks.

"Infections due to highly resistant bacteria are becoming
increasingly problematic," says Russo. "We are continually
threatened by a 'post-antibiotic' era. The combination of a
bacterium that is both highly virulent and resistant to
antimicrobials is double-trouble."

The researchers' concern stems from the fact that classical
Klebsiella pneumoniae is one of the bacterial species that
can easily acquire mobile genetic units, called plasmids, that
contain multiple genes that confer high levels of antimicrobial
resistance.

"That's in part why we're concerned," says Russo. "We know that
this bacterium has the potential to acquire these plasmids and it
almost certainly will."

He notes that most bacteria that have proven to be resistant to
most or all of the drugs currently available do not usually infect
healthy members of the community.

"What is alarming about the hypervirulent Klebsiella
pneumoniae is that they do possess the potential to infect
healthy people," says Russo. "If this hypervirulent bacterium also
becomes highly resistant to antimicrobials, we will have a
significant problem to manage. We hope that our research and that
of others can prevent this possibility."

While the new hypervirulent variant was first seen exclusively
in in the Pacific Rim, it has now been found in several cities in
North America, including Buffalo, and in Europe, Canada, Israel and
South Africa as well. The UB researchers characterize it as
"under-recognized" both by physicians and microbiology
laboratories.

The disease most commonly presents as a liver abscess, which is
not typical for otherwise healthy patients.

"This new variant presents with unique and scary features: first
is its tendency to infect young, healthy people in the community
and the second is its unique propensity for metastatic spread to
other parts of the body," says Russo. "It spreads to sites beyond
the initial source of the infection, such as the lungs, the central
nervous system and the eye, potentially causing loss of vision. If
infection spreads to the brain, there can be brain damage as well.
Between 10 and 30 percent of cases are fatal."

In Buffalo, this hypervirulent variant of Klebsiella
pneumoniae was identified in an otherwise healthy, young person
several years ago. The patient, who was in his 20s, was
hospitalized for several months before making a full recovery.
Similar cases are causing concern throughout the international
infectious disease community.

At the moment, most cases of hypervirulent Klebsiella
pneumoniae resolve if treated aggressively with antibiotics and
drainage of abscesses; however, some infections, despite optimal
treatment, result in a persistent morbidity or death, Russo
says.

He notes that the potential for the bug to acquire drug
resistance is adding a sense of urgency to the research.

Russo says that microbiology labs should be aware that an
important characteristic of these hypervirulent strains (also known
as hypermucoviscous strains) is that when bacterial colonies grown
on a solid surface in the laboratory are stretched by a common
microbiology tool, called an inoculation loop, they form a viscous
"string" greater than 5 millimeters in length.

Russo's team at UB is now beginning to develop a clearer picture
of this formidable bacterial opponent.

In November, he and his colleagues published a PLoS ONE paper
that showed that hypervirulent Klebsiella pneumoniae
acquires iron more efficiently than the usual strains of K.
pneumoniae.

"With the NIH grant, we hope to further elucidate the precise
details of the bacterial factors that are responsible for
hypervirulent Klebsiella pneumoniae acquiring iron so much
more efficiently," he says. "The goal of this line of research is
that these iron-acquisition factors possessed by hypervirulent
Klebsiella pneumoniae will then lend themselves as
therapeutic or vaccine targets so that we can better treat or
prevent infection."

In addition to Russo, other UB researchers working on
hypervirulent Klebsiella pneumoniae are Alyssa S. Shon, an
Infectious Diseases Fellow in the Department of Medicine; Janet
Beanan, Ulrike MacDonald, Daniel Metzger and Ruth Olson, all
research technicians in the Department of Medicine, and Alex
Pomakov, a UB undergraduate majoring in biomedical sciences. Mark
P. Visitacion, MD, a former Infectious Diseases Fellow in the UB
Department of Medicine, was also part of the team.